The aim of this ongoing project is to identify those specific receptors in brain, which are responsible for the reinforcing properties of nicotine. These properties will be measured by the techniques of discriminative cueing and self-administration. In addition, specific binding sites in brain membranes will be sought and their regional distribution in brain will be studied. By studying structure-activity relationships for variety of agonists and antagonists, we hope to obtain evidence for the identify of the binding sites and the receptors mediating the reinforcing properties of nicotine. Discriminative cueing and self-administration by microinjection into regions of high receptor density will also be studied. An isolated smooth muscle preparation, the longitudinal muscle strip from rat terminal colon, will be studied as an analog system to the nicotine receptors in brain.